(a). Field of the Invention
This invention relates to gastric cytoprotection in oral administration of aspirin.
(b). Information Disclosure Statement
Takagi et al in U.S. Pat. No. 3,988,466, issued Oct. 26, 1977, show that gastric lesions induced by aspirin or indomethacin are prevented by administration of amino acids, in particular, L-glutamine, L-lysine and L-arginine.
Goldenberg et al in U.S. Pat. No. 4,016,268, issued Apr. 5, 1977, show that bismuth subsalicylate co-administered with aspirin or other antiinflammatory drugs combats gastric ulceration associated with such drugs.
Seifter et al in U.S. Pat. No. 4,491,574, issued Jan. 1, 1985 show the use of the vitamin A or precursor thereof in a method of reducing toxicity and inhibiting ulcerogenesis and bleeding in the stomach of a mammal due to the ingestion of aspirin. This reference also cites a number of other publications pertaining to various means for inhibiting the gastric ulcerogenic effects of aspirin or other antiinflammatory agents, e.g., indomethacin.
Sodium thiosulfate, as shown in THE MERCK INDEX, Eighth Edition, 1968, pages 967-8, in addition to having a wide variety of non-medicinal uses, has been used as an antidote for cyanide poisoning, in some thrombotic conditions, topically for tinea versicolor, and, formerly for arsenical dermatitis. Also, it is said to have low human toxicity. As shown in THE MERCK INDEX, Tenth Edition, 1983, item 8542 (p. 1243), sodium thiosulfate is said to be useful in various veterinary indications in cats, e.g., antidote in cyanide poisoning, as a "general detoxifier", in bloat, and externally in ringworm, mange.
Fasth et al, Biochemical Pharmacology 22, 1337-1351 (1973), published a paper entitled "Protective Effect of Thiosulfate and metabolic Thiosulfate Precursors Against Toxicity of Nitrogen Mustard (HN.sub.2)".
Van Moorleghem French Patent Publication No. 2,318,649, published Feb. 18, 1977, pertains to medicaments containing bisublimed iodine, sodium or potassium iodide, an alkaline salt, a plasma substitute, an analgesic, anti-inflammatory and antipyretic, and an anesthetic agent, said medicaments useful for the treatment of rheumatism and cancer. A typical composition was prepared from the following solutions: 0.10 g iodine and 0.20 g of potassium iodide dissolved in 2 ml of water (soln. A); 0.266 g of magnesium thiosulfate in 2 ml of water (soln. B); 5 ml. of 25% polyvinyl pyrrolidone (soln. C); 0.5 g of aspirin and 0.05 g of sodium glycerophosphate in 5 ml of water (soln. D); and, 0.05 g of diethylamino 2,6-dimethylacetanilide hydrochloride, 5 mg of methyl p-hydroxybenzoate and an excipient to 5 ml (soln. E). Solutions A and B were mixed together until decolorized and solutions C, D and E added.